Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans

Abstract

Background-During the interdigestive state in humans, erythromycin 40 mg induces a premature activity front that starts in the stomach, while erythromycin 200 mg induces a prolonged period of enhanced antral contractile activity. Aims-To study the involvement of a cholinergic pathway in the motor eVects of erythromycin using the muscarinic antagonist atropine and the neural 5-HT 1 receptor agonist sumatriptan. Methods-In 30 healthy volunteers, fasted antroduodenojejunal motor activity was studied by stationary manometry. Placebo (n=10), atropine (15 µg/kg intravenous bolus plus 15 µg/kg/h over 30 minutes; n=10), or sumatriptan (6 mg subcutaneously; n=10) was administered, followed by infusion of erythromycin 40 mg or 200 mg. Results-After placebo, erythromycin 40 mg induced a premature activity front with gastric onset after 19.1 (1.7) minutes in all volunteers. After atropine, erythromycin 40 mg failed to induce a premature activity front during a 60 minute period in all volunteers (p<0.001), while sumatriptan prevented the induction of a premature activity front during a 60 minute period in all but one volunteer (p<0.005). The number of antral contractions and their mean amplitude in the 60 minutes after erythromycin 200 mg did not diVer significantly after atropine or sumatriptan versus placebo. Conclusions-The antral motor eVects of erythromycin in humans are mediated via diVerent pathways. The induction of a premature activity front is mediated through activation of an intrinsic cholinergic pathway, while the induction of enhanced antral contractile activity may be mediated via a pathway potentially involving activation of a muscular receptor. (Gut 1998;43:395-400)

Interaction of the Growth Hormone-Releasing Peptides Ghrelin and Growth Hormone-Releasing Peptide-6 with the Motilin Receptor in the Rabbit Gastric Antrum

“…Coulie et al (1998) noted that atropine failed to block the prolonged rhythmic antral contractile activity induced by high doses of erythromycin and suggested that it might be due to activation of smooth muscle motilin receptors, which have a lower affinity (Van Assche et al, 1997). However, as the present study indicates, it might also reflect the activation of a noncholinergic neural pathway.…”

“…In vivo studies in humans indicated that the effect of motilin and the motilin agonist erythromycin on antral motor activity is mediated through the activation of cholinergic neurons (Boivin et al, 1997;Coulie et al, 1998). Coulie et al (1998) noted that atropine failed to block the prolonged rhythmic antral contractile activity induced by high doses of erythromycin and suggested that it might be due to activation of smooth muscle motilin receptors, which have a lower affinity (Van Assche et al, 1997).…”

Parallel Incidences of Sudden Infant Death Syndrome and Infantile Hypertrophic Pyloric Stenosis: A Common Cause?

“…14 Erythromycin induces strong nonpropagated gastric contractions when distributed in high doses, which may lead to hypertrophy of the pylorus. 15,16 In addition, several biochemical markers in the hypertrophied pyloric muscle have been studied, such as the neuronal nitric oxide. 17 The reported incidence figures of IHPS vary between 1.5 and 3.0 per 1000 live births.…”

Outpatient vs. Inpatient Gastric Emptying Studies: Does Admission Status Influence Findings?

“…Two broad classes of medication are known to affect gastric motility; prokinetic agents accelerate gastric transit whereas another group of medications slow gastric transit times. Known prokinetic medications include metoclopramide, domperidone, erythromycin and cholinergic medications such as bethanechol [14][15][16][17][18][19][20]. Medications known to slow gastric emptying include opioid narcotics, tramadol, tricyclic antidepressants, calcium channel blockers, dopamine agonists, octreotide, anticholinergics, clonidine, and phenothiazines [14,[21][22][23][24][25][26][27][28][29][30][31][32][33].…”